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1.
Food Chem ; 366: 130573, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311232

RESUMO

Based on a murine monoclonal antibody (mAb) against tiamulin (TML), an electrochemical immunosensor was proposed using silver-graphene oxide (Ag-GO) nanocomposites and gold nanocomposites (AuNPs) to detect tiamulin (TML). Due to the synergetic properties of Ag-GO nanocomposites and AuNPs, the conductivity of the immunosensor was significantly enhanced. On account of the specific mAb and conductive nanocomposites, the proposed electrochemical immunosensor exhibited a low LOD of 0.003 ng mL-1 for the detection of TML in a wide linear range of 0.01 to 1000 ng mL-1. In addition, the immunosensor did not involve additional redox species. Furthermore, the efficient and simple electrochemical immunosensor was employed to detect TML in real samples with high accuracy, suggesting a potential detection platform for other veterinary antibiotics in animal derived foods.


Assuntos
Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Nanocompostos , Animais , Anticorpos Monoclonais , Diterpenos , Técnicas Eletroquímicas , Ouro , Imunoensaio , Limite de Detecção , Camundongos
2.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4424-4432, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581046

RESUMO

The chemical constituents from the roots of Aconitum kongboense were studied. Twenty-five diterpenoid alkaloids were isolated from the 95% methanol extract of the roots of A. kongboense by silica gel, reverse-phase silica gel and basic alumina column chromatography. They included a new aconitine-type diterpenoid alkaloid, named as kongboensenine(1), and twenty-four known ones(2-25), i.e., acotarine F(2), acotarine G(3), 14-acetyltalatisamine(4), talatisamine(5), indaconitine(6), yunaconitine(7), chasmanine(8), 6-epi-foresticine(9), homochasmanine(10), 8-deacetyl-yunaconitine(11), chasmaconitine(12), ajaconine(13), franchetine(14), ezochasmanine(15), crassicautine(16), 14-O-deacylcrassicausine(17), genicunine A(18), falconeridine(19), sachaconitine(20), liljestrandisine(21), 8-methyl-14-acetyltalatisamine(22), kongboendine(23), 14-benzoylchasmanine(24) and pseudaconine(25). Their structures were elucidated by common spectroscopic methods including high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and nuclear magnetic resonance(NMR) techniques. Compounds 2-4, 10, 13, 15-19 and 21-22 were isolated from this plant for the first time. Experimental results showed that all compounds did not have a significant inhibitory activity against acetylcholinesterase(AChE).


Assuntos
Aconitum , Alcaloides , Diterpenos , Acetilcolinesterase , Aconitum/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Raízes de Plantas/metabolismo
3.
Front Cell Infect Microbiol ; 11: 680127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527599

RESUMO

Since the first reported case caused by the novel coronavirus SARS-CoV-2 infection in Wuhan, COVID-19 has caused serious deaths and an ongoing global pandemic, and it is still raging in more than 200 countries and regions around the world and many new variants have appeared in the process of continuous transmission. In the early stage of the epidemic prevention and control and clinical treatment, traditional Chinese medicine played a huge role in China. Here, we screened out six monomer compounds, including artemether, artesunate, arteannuin B, echinatin, licochalcone B and andrographolide, with excellent anti-SARS-CoV-2 and anti-GX_P2V activity from Anti-COVID-19 Traditional Chinese Medicine Compound Library containing 389 monomer compounds extracted from traditional Chinese medicine prescriptions "three formulas and three drugs". Our discovery preliminary proved the stage of action of those compounds against SARS-CoV-2 and provided inspiration for further research and clinical applications.


Assuntos
COVID-19 , SARS-CoV-2 , Artemeter , Artemisininas , Artesunato , Chalconas , Diterpenos , Humanos
4.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500582

RESUMO

Salvia corrugata Vahl. is an interesting source of abietane and abeo-abietane compounds that showed antibacterial, antitumor, and cytotoxic activities. The aim of the study was to obtain transformed roots of S. corrugata and to evaluate the production of terpenoids in comparison with in vivo root production. Hairy roots were initiated from leaf explants by infection with ATCC 15834 Agrobacterium rhizogenes onto hormone-free Murashige and Skoog (MS) solid medium. Transformation was confirmed by polymerase chain reaction analysis of rolC and virC1 genes. The biomass production was obtained in hormone-free liquid MS medium using Temporary Immersion System bioreactor RITA®. The chromatographic separation of the methanolic extract of the untransformed roots afforded horminone, ferruginol, 7-O-acetylhorminone and 7-O-methylhorminone. Agastol and ferruginol were isolated and quantified from the hairy roots. The amount of these metabolites indicated that the hairy roots of S. corrugata can be considered a source of these compounds.


Assuntos
Abietanos/química , Diterpenos/química , Raízes de Plantas/química , Salvia/química , Agrobacterium/química , Agrobacterium/genética , Biomassa , Reatores Biológicos , Meios de Cultura/química , Raízes de Plantas/genética , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/genética , Salvia/genética , Transformação Genética/genética
5.
Phytomedicine ; 92: 153739, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34592488

RESUMO

BACKGROUND: Triptolide is naturally isolated from Tripterygium wilfordii Hook F., possessing multiple biological activities. Hepatotoxicity is one of the main side effects of triptolide. However, the effect of triptolide on nonalcoholic fatty liver disease remains unknown (NAFLD). PURPOSE: This study aimed to observe the amelioration of triptolide against NAFLD and investigate the engaged mechanism. METHODS: Two typical animal models of NAFLD, obese db/db mice and methionine/choline-deficient (MCD) diet-fed mice, were used. Hepatic steatosis, inflammation, and fibrosis were evaluated by H&E and Masson staining. Oil red O staining and lipid extraction analysis were used to detect fat content in mice livers. Expression of lipid metabolism, inflammatory and fibrogenic genes was also detected by Real-time PCR and Western blotting, respectively. Phosphoproteomics, molecular docking, and TR-FRET assay were performed to provide further insight into how triptolide improved NAFLD. RESULTS: Intraperitoneal injection of triptolide at a daily dose of 50 µg/kg significantly alleviated MCD diet-induced nonalcoholic steatohepatitis (NASH), but 100 µg/kg triptolide caused severe hepatotoxicity. Pathological staining confirmed low-dose triptolide treatment reducing hepatic lipid deposition, inflammation, and fibrosis in NASH. Serum biochemical analysis revealed a reduction in the level of liver enzymes and bilirubin. MCD also induced rising expression of typical genes and proteins related to fibrosis (fibronectin, α-SMA, collagens, TGF-ß) and inflammation (ILs, TNF-α, MCP-1), which was suppressed by low-dose triptolide. Data from the proteomics/phosphoproteomics and TR-FRET assay indicated triptolide was a potential allosteric AMPK agonist to increase the phosphorylation on Thr172 residue, with the EC50 of 277.78 µM and 231.02 µM for AMPKα1 and AMPKα2, respectively. Moreover, triptolide exhibited an ability to activate AMPK and further led to increasing ACC1 phosphorylation in the liver. The positive results that triptolide ameliorated hepatic lipogenesis, fatty acid oxidation, and fibrosis of NAFLD via activating AMPK were further confirmed in db/db mice with 10-week intervention (50 µg/kg, i.v., twice a week). CONCLUSION: This study demonstrates that dose-related triptolide as an allosteric AMPK agonist has the potential to alleviate NAFLD without hepatotoxicity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Diterpenos , Compostos de Epóxi , Inflamação/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fenantrenos
6.
Chem Pharm Bull (Tokyo) ; 69(9): 913-917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470956

RESUMO

Two new trihydroxy derivative of Δ8(14),15-isopimarane diterpenoids, shanpanootols G (1) and H (2), along with three known analogues were isolated from the ethyl acetate-soluble extract of Kaempferia pulchra rhizomes collected in Shan State of Myanmar. The structures of these compounds including their absolute configurations were elucidated by the combination of one dimensional (1D) and 2D-NMR spectroscopic methods, high resolution mass spectrometric technique, and the experimental and the calculated electronic circular dichroism (ECD) data. The isopimarane diterpenoids (1-5) were tested for their Viral protein R (Vpr) inhibitory activities against TREx-HeLa-Vpr cells. Shanpanootol H (2) and (1R,2S,5S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15-dien-7-one (4) exhibited anti-Vpr activities at the 5 µM treated dose.


Assuntos
Diterpenos/farmacologia , Rizoma/química , Zingiberaceae/química , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Diterpenos/química , Diterpenos/isolamento & purificação , Conformação Molecular , Mianmar , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo
7.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500601

RESUMO

Kahweol is a diterpene molecule found in coffee that exhibits a wide range of biological activity, including anti-inflammatory and anticancer properties. However, the impact of kahweol on pancreatic ß-cells is not known. Herein, by using clonal rat INS-1 (832/13) cells, we performed several functional experiments including; cell viability, apoptosis analysis, insulin secretion and glucose uptake measurements, reactive oxygen species (ROS) production, as well as western blotting analysis to investigate the potential role of kahweol pre-treatment on damage induced by streptozotocin (STZ) treatment. INS-1 cells pre-incubated with different concentrations of kahweol (2.5 and 5 µM) for 24 h, then exposed to STZ (3 mmol/L) for 3 h reversed the STZ-induced effect on cell viability, apoptosis, insulin content, and secretion in addition to glucose uptake and ROS production. Furthermore, Western blot analysis showed that kahweol downregulated STZ-induced nuclear factor kappa B (NF-κB), and the antioxidant proteins, Heme Oxygenase-1 (HMOX-1), and Inhibitor of DNA binding and cell differentiation (Id) proteins (ID1, ID3) while upregulated protein expression of insulin (INS), p-AKT and B-cell lymphoma 2 (BCL-2). In conclusion, our study suggested that kahweol has anti-diabetic properties on pancreatic ß-cells by suppressing STZ induced apoptosis, increasing insulin secretion and glucose uptake. Targeting NF-κB, p-AKT, and BCL-2 in addition to antioxidant proteins ID1, ID3, and HMOX-1 are possible implicated mechanisms.


Assuntos
Café/química , Diterpenos/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Antioxidantes , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia
8.
Appl Microbiol Biotechnol ; 105(20): 7683-7694, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34568965

RESUMO

Andrographis paniculata (AP) is a medicinal plant that is traditionally used in Indian, Chinese, Malay, Thai, and Oriental system of medicines to treat various disorders. AP consists of andrographolide (AD), 14-deoxy-11,12-didehydroandrographolide (DDAD), and neoandrographolide (NAD) as major diterpene lactones which has extremely bitter properties; therefore, AP is commonly called "King of bitters." AD, DDAD, and NAD are reported to possess therapeutic values such as antioxidant, immunostimulatory, hepatoprotective, anti-cancer, anti-inflammatory, anti-rheumatoidal, anti-malarial, anti-leishmanial, anti-fertility, anti-obesity, antipyretic, and antimicrobial attributes. According to the Indian Pharmacopoeia, the leaves and tender shoots of AP yield up to 1%, 0.16%, and 0.11% of AD, DDAD, and NAD, respectively, on a dry-weight basis. However, variability in the accumulation of AD, DDAD, and NAD in plants has been reported with respect to species, genotype, season, phenological stage, plant part used, and geography of a region of cultivation. Therefore, cell and tissue culture systems especially cell, shoot, and adventitious root cultures are explored as alternatives for constant and higher production of AD, DDAD, and NAD. This review explores the prospects of exploiting the plant cell and tissue culture systems for the controlled production of AD, DDAD, and NAD. Various strategies such as elicitation by using biological and chemical elicitors are explored for the enhancement of accumulation of AD, DDAD, and NAD in cell and organ cultures. KEY POINTS: • This review explores the possibilities of diterpene lactone production from cell and organ cultures. • Various strategies are explored for the enhanced accumulation of AD, DDAD, and NAD in cell and organ cultures. • Prospects of diterpene lactone production are highlighted.


Assuntos
Andrographis , Diterpenos , Lactonas , Técnicas de Cultura de Órgãos , Extratos Vegetais , Folhas de Planta
9.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4139-4144, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467725

RESUMO

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-ß-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.


Assuntos
Callicarpa , Diterpenos , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Folhas de Planta
10.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3789-3796, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472251

RESUMO

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.


Assuntos
Diterpenos , Sesquiterpenos , Compostos Fitoquímicos/farmacologia , Plantas , Sesquiterpenos/farmacologia , Terpenos
11.
Phytochemistry ; 191: 112902, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34384921

RESUMO

Thirteen undescribed diterpenoid quinones were isolated from the dried roots of Salvia miltiorrhiza. Their structures were determined by extensive analysis, including NMR, HRESIMS, and IR. Their absolute configurations were determined by X-ray diffraction, calculated and experimental circular dichroism spectroscopy, and optical rotation. In the evaluation of bioactivities, salviadionether obviously inhibited the proliferation of HCT-116 cells. R-(+)-salmiltiorin E and R-(+)-grandifolia D both showed inhibitory activities on a variety of tumor cells. Salvianone ester A showed strong cytotoxicity to tumor-repopulating cells (TRCs) with an IC50 value of 2.19 µM.


Assuntos
Diterpenos , Salvia miltiorrhiza , Salvia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas , Quinonas/farmacologia , Rizoma
12.
J Org Chem ; 86(17): 11771-11781, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34338508

RESUMO

Litosetoenins A-E (1-5), five new ring-rearranged serrulatane-type diterpenoids with a common tricyclo[3.0.4]decane core, along with a known diterpenoid glycoside (6), a related known diterpenoid (7), and four known sesquiterpenoids (8-11), were isolated from a Balinese soft coral Litophyton setoensis. Spirolitosetoenin A (5a) and isospirolitosetoenin A (5b), featuring an unprecedented spiro[4,5]decane core, were obtained after treatment of compound 5 with HCl in methanol. The structures of new compounds were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical methods. A plausible biosynthetic pathway involving an unusual divergent biogenesis was proposed.


Assuntos
Antozoários , Diterpenos , Sesquiterpenos , Animais , Ciclização , Compostos de Epóxi , Estrutura Molecular
13.
Int Endod J ; 54(11): 2099-2112, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34375451

RESUMO

AIM: To evaluate whether treatment with resiniferatoxin (RTX) is capable of lowering the plasma levels of PGE2 and TNF-α, as well as histopathological parameters in inflammation of pulp tissue in a mouse experimental model. METHODOLOGY: Ten groups of six BALB/c mice were formed as follows: healthy group (HC ), healthy group treated with RTX (HRTX ), two groups with pulp inflammation at 14 and 18 hours (PI14 /PI18 ), six groups with pulpal inflammation plus treatment with Ibuprofen (IBU14 /IBU18 ), dexamethasone (DEX14 /DEX18 ) and resiniferatoxin (RTX14 /RTX18 ) at 14 and 18 hours, respectively. Pulpal inflammation was induced through occlusal exposure of the pulp of the maxillary first molar. The plasma levels of PGE2 and TNF-α and the histological parameters of the pulp tissue of the HC and HRTX groups were evaluated at the time of acquiring the animals. In the other groups, the plasma levels of PGE2 and TNF-α and the histopathological parameters were evaluated at 14 and 18 hours after pulp damage. Plasma levels of PGE2 and TNF-α were quantified by ELISA, and the histopathological parameters were evaluated by H/E staining. Statistical significance was determined by one-way analysis of variance (ANOVA) to test for overall differences between group means. RESULTS: A significant increase (*p < .05) in plasma levels of PGE2 and TNF-α occurred 14 and 18 hours after pulp damage. In addition, treatment with RTX significantly decreased (*p < .05) the plasma levels of PGE2 and TNF-α at 14 and 18 hours after pulp damage, as well as the infiltrate of inflammatory cells at 18 hours after pulp damage, similarly to treatment with ibuprofen and dexamethasone. CONCLUSION: It was possible to detect systemic levels of PGE2 and TNF-α at 14 and 18 hours after pulp damage. Likewise, treatment with RTX was associated with an anti-inflammatory effect similar to treatment with ibuprofen and dexamethasone. These findings place resiniferatoxin as a therapeutic alternative in the treatment of inflammatory diseases in Dentistry.


Assuntos
Polpa Dentária/patologia , Diterpenos , Inflamação/tratamento farmacológico , Animais , Polpa Dentária/efeitos dos fármacos , Diterpenos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Teóricos , Fator de Necrose Tumoral alfa
14.
Molecules ; 26(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443641

RESUMO

Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure-activity relationships for the period covering 2013-2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10-50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure-activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Descoberta de Drogas/métodos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade
15.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361785

RESUMO

Even today, weeds continue to be a considerable problem for agriculture. The application of synthetic herbicides produces serious environmental consequences, and crops suffer loss of their activity due to the appearance of new resistant weed biotypes. Our aim is to develop new effective natural herbicides that improve the problem of resistance and do not harm the environment. This work is focused on a bioassay-guided isolation and the characterization of natural products present in Moquiniastrum pulchrum leaves with phytotoxic activity and its preliminary application in weeds. Moquiniastrum pulchrum was selected for two reasons: it is an abundant species in the Cerrado region (the second most important ecosystem in Brazil, after the Amazon)-the explanation behind its being a dominant species is a major focus of interest-and it has traditional employment in folk medicine. Six major compounds were isolated in this plant: one flavone and five diterpenes, two of which are described for the first time in the literature. Four of the six compounds exhibited phytotoxic activity in the bioassays performed. The results confirmed the phytotoxic potential of this plant, which had not been investigated until now.


Assuntos
Asteraceae/química , Agentes de Controle Biológico/toxicidade , Diterpenos/toxicidade , Flavonas/toxicidade , Herbicidas/toxicidade , Plantas Daninhas/efeitos dos fármacos , Controle de Plantas Daninhas/métodos , Bioensaio , Agentes de Controle Biológico/química , Agentes de Controle Biológico/isolamento & purificação , Produtos Agrícolas/crescimento & desenvolvimento , Diterpenos/química , Diterpenos/isolamento & purificação , Flavonas/química , Flavonas/isolamento & purificação , Herbicidas/química , Herbicidas/isolamento & purificação , Humanos , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Plantas Daninhas/crescimento & desenvolvimento
16.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361662

RESUMO

Erinacine A, derived from the mycelia of Hericium erinaceus, has attracted much attention due to its neuroprotective properties. However, very few studies have been conducted on the bioavailability, tissue distribution, and protein binding of erinacine A. This study aimed to investigate the bioavailability, tissue distribution, and protein binding of erinacine A in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 2.381 g/kg BW of the H. erinaceus mycelia extract (equivalent to 50 mg/kg BW of erinacine A) and 5 mg/kg BW of erinacine A, respectively, the absolute bioavailability of erinacine A was estimated as 24.39%. Erinacine A was detected in brain at 1 h after oral dosing and reached the peak at 8 h. Protein binding assay showed unbound erinacine A fractions in brain to blood ratio is close to unity, supporting passive diffusion as the dominating transport. Feces was the major route for the elimination of erinacine A. This study is the first to show that erinacine A can penetrate the blood-brain barrier of rats by the means of passive diffusion and thus support the development of H. erinaceus mycelia for the improvement of neurohealth.


Assuntos
Diterpenos/metabolismo , Diterpenos/farmacocinética , Hericium/química , Micélio/química , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Intravenosa , Administração Oral , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Cromatografia Líquida/métodos , Diterpenos/administração & dosagem , Fezes/química , Masculino , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
17.
Toxicol Appl Pharmacol ; 428: 115672, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34391754

RESUMO

5-Fluorouracil (5-FU)-based chemotherapy is the first-line recommended regimen in colorectal cancer (CRC), but resistance limits its clinical application. Andrographolide sulfonate, a traditional Chinese medicine, is mainly used to treat infectious diseases. In the present study, we reported that andrographolide sulfonate could significantly inhibit the growth of transplanted CT26 colon cancer in mice and improve survival when combined with 5-FU. Furthermore, TUNEL assay and immunohistochemistry analysis of proliferating cell nuclear antigen, Ki-67 and p-STAT3 confirmed that co-treatment could inhibit tumor proliferation and promote apoptosis. In tumor tissues of groups that received 5-FU and andrographolide sulfonate, CD4+ and CD8+ T cell infiltration was increased, and the expression of IFN-γ and Granzyme B detected by immunohistochemistry and qPCR was upregulated, reflecting improved antitumor immunity. Finally, we verified that 5-FU significantly activated the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in myeloid-derived suppressor cells (MDSCs) and that andrographolide sulfonate reversed this process to sensitize cells to 5-FU. In summary, andrographolide sulfonate synergistically enhanced antitumor effects and improved antitumor immunity by inhibiting 5-FU-induced NLRP3 activation in MDSCs. These findings provide a novel strategy to address 5-FU resistance in the treatment of CRC.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Diterpenos/administração & dosagem , Fluoruracila/administração & dosagem , Células Supressoras Mieloides/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
18.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445570

RESUMO

Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation targets. First, the cytotoxicity of kahweol was checked by 3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, while 2,20-azino-bis (3ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1-diphenyl-2-picryl-hydrazyl were used to examine the radical scavenging ability. Polymerase chain reaction analysis was performed to explore the proper time points and doses affecting skin hydration and barrier-related genes. Luciferase assay and Western blotting were used to explore the possible transcription factors. Finally, fludarabine (a STAT1 inhibitor) was chosen to discern the relationship between skin-moisturizing factors and STAT1. We found that HaCaT cells experienced no toxicity from kahweol, and kahweol displayed moderate radical scavenging ability. Moreover, kahweol increased the outcome of HAS1, HAS2, occludin, and TGM-1 from six hours in a dose-dependent manner as well as the activation of STAT1 from six hours. Additionally, kahweol recovered the suppression of HAS2, STAT1-mediated luciferase activity, and HA secretion, which was all downregulated by fludarabine. In this study, we demonstrated that kahweol promotes skin-moisturizing activities by upregulating STAT1.


Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Queratinócitos/fisiologia , Fator de Transcrição STAT1/metabolismo , Pele/efeitos dos fármacos , Apoptose , Proliferação de Células , Células Cultivadas , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Fator de Transcrição STAT1/genética
19.
Phytochemistry ; 191: 112926, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34425461

RESUMO

Two seco-norabietane diterpenes with unique structures, namely abrotafuran and abrotacid, were isolated from the roots of Salvia abrotanoides (Kar.) Sytsma. The compounds were characterized by 1D and 2D NMR spectroscopic techniques, ECD, and HR-ESIMS experiments. Plausible biosynthetic pathways of abrotafuran and abrotacid were proposed. These compounds did not exhibit antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. However, the rearranged seco-norabietane abrotafuran showed antiproliferative activity on HeLa (cervical carcinoma) and Jurkat (T-cell leukemia) cell lines.


Assuntos
Diterpenos , Salvia , Abietanos/farmacologia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas , Esqueleto
20.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3249-3256, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396744

RESUMO

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Diterpenos , Fenantrenos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Diterpenos/farmacologia , Compostos de Epóxi , Feminino , Humanos , Microambiente Tumoral
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